Related Experiment Video
Updated: Feb 17, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Next-Generation Sequencing Approach to Non-Small Cell Lung Carcinoma Yields More Actionable Alterations
Mitra Mehrad, Somak Roy, Humberto Trejo Bittar
1From the Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (Dr Mehrad); and the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Drs Roy, Trejo Bittar, and Dacic).
Context:
- Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance.
Objective:
- To determine the best testing algorithm for patients with lung cancer in our clinical practice.
Design:
- Two testing approaches for metastatic lung adenocarcinoma were offered between 2012-2015. One approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK, ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the 8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel.
Results:
- Of 1200 non-small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29 adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%) in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of 29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2 LCNECs showed investigational genomic alterations.
Conclusions:
- The NGS approach would result in the identification of a significant number of actionable gene alterations, increasing the therapeutic options for patients with advanced NSCLCs.
